A novel iris transillumination grading scale allowing flexible assessment with quantitative image analysis and visual matching.

PURPOSE: To develop a sensitive scale of iris transillumination suitable for clinical and research use, with the capability of either quantitative analysis or visual matching of images. METHODS: Iris transillumination photographic images were used from 70 study subjects with ocular or oculocutaneous albinism. Subjects represented a broad range of ocular pigmentation. A subset of images was subjected to image analysis and ranking by both expert and nonexpert reviewers. Quantitative ordering of images was compared with ordering by visual inspection. Images were binned to establish an 8-point scale. Ranking consistency was evaluated using the Kendall rank correlation coefficient (Kendall's tau). Visual ranking results were assessed using Kendall's coefficient of concordance (Kendall's W) analysis. RESULTS: There was a high degree of correlation among the image analysis, expert-based and non-expert-based image rankings. Pairwise comparisons of the quantitative ranking with each reviewer generated an average Kendall's tau of 0.83 ± 0.04 (SD). Inter-rater correlation was also high with Kendall's W of 0.96, 0.95, and 0.95 for nonexpert, expert, and all reviewers, respectively. CONCLUSIONS: The current standard for assessing iris transillumination is expert assessment of clinical exam findings. We adapted an image-analysis technique to generate quantitative transillumination values. Quantitative ranking was shown to be highly similar to a ranking produced by both expert and nonexpert reviewers. This finding suggests that the image characteristics used to quantify iris transillumination do not require expert interpretation. Inter-rater rankings were also highly similar, suggesting that varied methods of transillumination ranking are robust in terms of producing reproducible results.

Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury.

Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.

Placental Characteristics of Fetuses With Congenital Heart Disease.

OBJECTIVES: To investigate whether there is an association between congenital heart disease (CHD) and placental abnormalities. METHODS: We conducted a case-control study that included cases of infants with CHD who underwent cardiac surgery within 6 months of life at the Johns Hopkins Medical Center from 2000 to 2013, and gestational age-matched normal pregnancy controls (200 neonates per group). RESULTS: Overall, abnormal placental cord insertion (ie, eccentric, marginal, or velamentous) was associated with CHD (odds ratio, 2.33-3.76). The main cardiac defects associated with abnormal cord insertion were conotruncal defects (relative risk, 3.08; 95% confidence interval [CI], 1.48-6.40; P = .003), left heart disease (relative risk, 2.40; 95% CI, 1.32-4.37; P = .004), and right heart disease (relative risk, 2.22; 95% CI, 1.21-4.07; P = .010). The Placenta-to-birth weight ratio was not associated with CHD. Intrauterine growth restriction was associated with CHD (odds ratio, 3.00; 95% CI, 1.41-6.39; P = .004). CONCLUSIONS: Abnormal cord insertion, as well as intrauterine growth restriction, was determined to be correlated with the presence of CHD. On the basis of our results, we conclude that cord insertion should be evaluated at routine obstetric sonography, and further fetal heart evaluation is warranted if abnormal cord insertion is detected.

Tuberculous meningitis in adults: a review of a decade of developments focusing on prognostic factors for outcome.

Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment, mortality and long-term disability remain unacceptably high. Prevention, early recognition, diagnosis and treatment are fundamental to improving outcomes. However, an effective vaccine remains elusive, initial symptoms are nonspecific, and sensitive diagnostic tests are not available. There has been progress in our understanding of the immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on presentation, seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and lactate levels, hyponatreamia and coinfection with HIV are all found to be important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence susceptibility to TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic tests, novel insights into pathogenesis and an increasing evidence base for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines.